Disease relevance of Ren1

• Chimeric genes containing the 5'-flanking regions of the mouse renin genes, Ren1 and Ren2, associated with the early region of the simian virus 40 (SV40) were constructed [1].
• Specific high-titer antibodies to rat kidney renin were raised using pure rat kidney renin conjugated with tetanus toxoid as antigen [2].
• Ren1c(-/-) mice are lean, insulin sensitive, and resistant to diet-induced obesity without changes in food intake and physical activity [3].

High impact information on Ren1

• This has encouraged intense activity in the development of inhibitors of kidney renin, which is a very specific aspartic proteinase catalysing the first and rate limiting step in the conversion of angiotensinogen to angiotensin II [4].
• Ren2d but not Ren1d is expressed in submandibular gland (SMG) while both are expressed in the kidney [5].
• Contrary to the SMG, transfection with Ren1d fragment-CAT construct or Ren2d fragment-CAT construct into the kidney resulted in similar levels of CAT expression [5].
• Fragments of the Ren1d or Ren2d promoter were fused to a chloramphenicol acetyltransferase (CAT) gene expression vector [5].
• Comparison of these sequences with the sequence of Swiss mouse SMG renin mRNA we have previously reported, demonstrates that Swiss mice express the two non-allelic genes, Rn1 and Rn2 [6].

Biological context of Ren1

• Nucleotide sequence of a cDNA coding for mouse Ren1 preprorenin [7].
• Southern analysis of mice from the second generation revealed that the mutant Ren1 and Ren2 were interchromosomally recombined at the loxP sites to produce a new dually mutated allele on the chromosome at the rate of 9.6% (7/73) [8].
• In contrast, kidney renin levels appear to be unaffected by the gene duplication [9].
• Moreover, a single base substitution of A for G at residue #996 in the kidney renin mRNA creates a potential glycosylation recognition site that may, in part, account for the differential glycosylation of kidney and submaxillary gland renins [9].
• We have previously shown that strains with high levels of SMG renin, such as Swiss or AKR mice, have two renin genes, Rn1 and Rn2, per haploid genome, while strains with low levels of SMG, such as BALB/c or C57Bl/6, have only one renin gene [6].

Anatomical context of Ren1

• The structural gene for mouse kidney renin (Ren-1) was localized to chromosome 1 by Southern blot analysis of mouse-hamster somatic cell hybrids with a cloned mouse submandibular renin cDNA probe [10].
• The two recombinant genes which contain, respectively, 0.45- and 2.5-kb the Ren1 and Ren2 5'-flanking sequences, named Ren1Tag and Ren2Tag, were microinjected into fertilized eggs [1].
• As shown by in vitro translation of full-length renin b mRNA in the presence of microsomal membranes, renin b was not targeted into the endoplasmatic reticulum and remained intracellularly in transiently transfected AtT-20 cells [11].
• Kidney renin transcripts were first detected at 14.5 days post coitum in the newly developing arteries in fetuses of both genotypes of mice [12].
• Spleen cells from mice immunized with partially purified hog kidney renin were fused with mouse myeloma cells to produce a stable monoclonal hybridoma cell line that synthesizes an antibody against renin [13].

Associations of Ren1 with chemical compounds

• Expression of the mouse renin genes (Ren1 and Ren2) in the submaxillary gland of female mice has been analyzed following administration of thyroxine (T4) or dihydrotestosterone (DHT) [14].
• Reversal of the suppressed kidney renin level in the hypertensive transgenic rat TGR(mRen-2)27 by angiotensin converting enzyme inhibition [15].
• On the other hand, the mouse antibody suppressed kidney renin in the untreated TGR(mRen-2)27 rats by only 11.0 +/- 3.3% (n = 6, P < .05), and did not suppress kidney renin in the perindopril treated TGR(mRen-2)27 rats (n = 6, P < NS) [15].
• Expression of endogenous renin and a renin-promoter controlled transgene in As4.1 cells, and kidney renin mRNA in C57BL/6J mice was induced after retinoid treatment [16].
• Hog kidney renin dissociates in the presence of sodium dodecyl sulfate (SDS) and mercaptoethanol to heavy and light chains with molecular weights of 33,700 and 5,800, respectively [13].
• Elements of signal transduction included endothelial Ca2+, the production of NO and prostaglandin (PGE2), and their paracrine actions on adjacent renin-producing cells [17].

Regulatory relationships of Ren1

• The data indicate that submandibular gland renin cross-reacts with kidney renin, but that genetic controls of these polypeptides in the two organs are independent [18].
• Integration of mouse Ren-2 gene into the rat genome led to fulminant hypertension despite suppressed plasma and kidney renin concentrations [19].

Other interactions of Ren1

• Ren1d and Ren2 cooperate to preserve homeostasis: evidence from mice expressing GFP in place of Ren1d [20].
• The uterine renin concentration at this stage of pregnancy was four-fold higher than that of the nonpregnant uterus but still less than 0.1% of the kidney renin concentration [21].

Analytical, diagnostic and therapeutic context of Ren1

• We now report the molecular cloning of cDNA copies of Swiss mouse kidney renin mRNA and present nucleotide sequence data of the recombinant clones [6].
• This conclusion is in agreement with a prior estimate based upon comparative sequence analysis of Ren-1 and Ren-2 from inbred laboratory mice [22].
• Immunochemical methods, Western blotting, direct radioimmunoassay, and immunoaffinity chromatography were used to isolate and identify rat kidney renin and prorenin and to determine their molecular weights without complete purification [23].
• In the kidney renin mRNA was increased 3.0-fold (+/- 0.30) by captopril, 2.3-fold (+/- 0.23) by a low sodium diet, and 1.7-fold (+/- 0.13) by spironolactone after 1 week, whereas T4, testosterone, or propylthiouracil had little or no effect [24].

References